The Drosophila Claudin Kune-kune Is Required for Septate Junction Organization and Tracheal Tube Size Control
The Drosophila Claudin Kune-kune Is Required for Septate Junction Organization and Tracheal Tube Size Control
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DOI：
10.1534/genetics.110.114959
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发表时间：
2010-07-01
期刊：
影响因子：
3.3
通讯作者：
Beitel, Greg J.
中科院分区：
文献类型：
--
作者：
Nelson, Kevin S.;Furuse, Mikio;Beitel, Greg J.
脊椎动物紧密连接是一种关键的基于claudin的细胞-细胞连接，其功能是阻止上皮细胞之间的自由细胞旁扩散。在果蝇中，这种屏障是由隔连接提供的，尽管隔连接在超微结构上与脊椎动物的紧密连接不同，但也含有Claudin家族蛋白Megatrachea和sinous。在这里，我们鉴定了第三种果蝇claudin，Kune-kune，它定位于分隔的连接，是连接组织和细胞旁屏障功能所必需的，但不是顶基极极性所必需的。在气管系统中，间隔连接具有不依赖屏障的功能，促进管腔分泌蠕形和蛇纹石，这是限制气管长度所需的细胞外基质调节蛋白。就像弯曲的和巨型气管一样，Kune-kune的缺失会阻止这种分泌，并导致过度延长的管子。缺乏这三个特征的Claudin的胚胎具有与任何单个突变体相似的气管表型，这表明这些Claudin在控制气管长度的相同途径中起作用。然而，我们发现，在上皮间隔连接的形成中，对这些Claudins有不同的要求。Megatrachea主要是正确定位间隔连接成分所必需的，而Sinous主要是维持间隔连接蛋白的正常水平所必需的。本地化和关卡都需要Kune-kune。SINVINE和Megatrachea与Kune-kune的双突变和三突变组合类似于Kune-kune单一突变体，这表明Kune-kune在隔膜连接的形成中比SINVING或Megatrachea起到更核心的作用。
The vertebrate tight junction is a critical claudin-based cell-cell junction that functions to prevent free paracellular diffusion between epithelial cells. In Drosophila, this barrier is provided by the septate junction, which, despite being ultrastructurally distinct from the vertebrate tight junction, also contains the claudin-family proteins Megatrachea and Sinuous. Here we identify a third Drosophila claudin, Kune-kune, that localizes to septate junctions and is required for junction organization and paracellular barrier function, but not for apical-basal polarity. In the tracheal system, septate junctions have a barrier-independent function that promotes lumenal secretion of Vermiform and Serpentine, extracellular matrix modifier proteins that are required to restrict tube length. As with Sinuous and Megatrachea, loss of Kune-kune prevents this secretion and results in overly elongated tubes. Embryos lacking all three characterized claudins have tracheal phenotypes similar to any single mutant, indicating that these claudins act in the same pathway controlling tracheal tube length. However, we find that there are distinct requirements for these claudins in epithelial septate junction formation. Megatrachea is predominantly required for correct localization of septate junction components, while Sinuous is predominantly required for maintaining normal levels of septate junction proteins. Kune-kune is required for both localization and levels. Double- and triple-mutant combinations of Sinuous and Megatrachea with Kune-kune resemble the Kune-kune single mutant, suggesting that Kune-kune has a more central role in septate junction formation than either Sinuous or Megatrachea.